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Abstract：
There is a growing interest in the discovery of novel xanthine oxidase inhibitors for gout prevention and treatment with fewer side effects. This study aimed to identify the xanthine oxidase (XO) inhibitory potential and drug-likeness of the metabolites present in the methanolic leaf extract of Anastatica (A.) hierochuntica L. using in vitro and in silico models. The extract-derived metabolites were identified by liquid-chromatography-quadrupole-time-of-flight-mass-spectrometry (LC-QTOF-MS). Molecular docking predicted the XO inhibitory activity of the identified metabolites and validated the best scored in vitro XO inhibitory activities for experimental verification, as well as predictions of their anticancer, pharmacokinetic, and toxic properties; oral bioavailability; and endocrine disruption using SwissADMET, PASS, ProTox-II, and Endocrine Disruptome web servers. A total of 12 metabolites, with a majority of flavonoids, were identified. Rutin, quercetin, and luteolin flavonoids demonstrated the highest ranked docking scores of -12.39, -11.15, and -10.43, respectively, while the half-maximal inhibitory concentration (IC50) values of these metabolites against XO activity were 11.35 µM, 11.1 µM, and 21.58 µM, respectively. In addition, SwissADMET generated data related to the physicochemical properties and drug-likeness of the metabolites. Similarly, the PASS, ProTox-II, and Endocrine Disruptome prediction models stated the safe and potential use of these natural compounds. However, in vivo studies are necessary to support the development of the prominent and promising therapeutic use of A. hierochuntica methanolic-leaf-extract-derived metabolites as XO inhibitors for the prevention and treatment of hyperuricemic and gout patients. Furthermore, the predicted findings of the present study open a new paradigm for these extract-derived metabolites by revealing novel oncogenic targets for the potential treatment of human malignancies.
摘要：
人们对发现用于痛风预防和治疗且副作用较少的新型黄嘌呤氧化酶抑制剂越来越感兴趣。这项研究旨在确定Anastatica甲醇叶提取物中存在的黄嘌呤氧化酶（XO）抑制潜力和代谢物的药物相似性（A.)使用体外和计算机模型。通过液相色谱-四极杆-飞行时间-质谱(LC-QTOF-MS)鉴定提取物衍生的代谢物。分子对接预测了鉴定的代谢物的XO抑制活性，并验证了最佳的体外XO抑制活性，以进行实验验证。以及对它们抗癌的预测，药代动力学，和毒性特性；口服生物利用度；和使用SwissADMET的内分泌干扰，通过,ProTox-II,和内分泌突变网络服务器。共有12种代谢物，含有大部分类黄酮，已确定。芦丁,槲皮素,和木犀草素类黄酮表现出最高的对接得分分别为-12.39、-11.15和-10.43，而这些代谢物对XO活性的半最大抑制浓度（IC50）值为11.35µM，11.1µM,和21.58µM，分别。此外,SwissADMET生成了与代谢物的理化性质和药物相似度相关的数据。同样，PASS,ProTox-II,和内分泌突变预测模型说明了这些天然化合物的安全和潜在用途。然而,体内研究是必要的,以支持开发突出和有前景的治疗用途。此外，本研究的预测结果为这些提取物衍生的代谢物开辟了一个新的范例，揭示了新的致癌靶标，可用于人类恶性肿瘤的潜在治疗。
